[转移帖]Immunity：里程碑的发现——B细胞抗病毒感染新机制

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原帖由#ipsvirus于2012-3-9 15:09发于老论坛

     如果你老板问你，B细胞如何发挥抗病毒作用呢？你可能会回答，效应B淋巴细胞产生的中和抗体可以抵抗病毒感染。你老板就会对你说，呵呵，骚年，你还是too young, too naive啊。

     最近由哈佛医学院的Ulrich von Andrian及圣拉斐尔科学研究所Matteo Iannacone组成的研究小组利用两种基因改造小鼠进行实验。uMT小鼠——B细胞缺失小鼠。DHLMP2A小鼠——B淋巴细胞产生抗体能力缺陷小鼠。研究人员对这两种突变小鼠和正常小鼠分别进行皮下注射VSV免疫反应，监测小鼠存活，并检测抗体及干扰素表达。结果如下图所示





     中和性抗体被认为是保护机体抵抗病毒所必须的，但现在证据显示并不一定是这样。DHLMP2A小鼠存活机制研究发现，当这种抗体缺陷小鼠感染VSV后，B淋巴细胞能产生一种化学物质淋巴毒素α1β2，而这种毒素能维持被膜下淋巴窦保护性巨噬细胞形态，使得其倾向优先被VSV感染。感染VSV的巨噬细胞分泌IFN-I，从而保护神经系统免受感染。在这一抵抗VSV感染过程中，抗体及获得性免疫病没有参与。



     这个发现说明免疫系统的第一道防线——天然免疫（包括巨噬细胞）在抵抗病毒感染过程中有着未被发现的功能。


     该研究得到NIH多项项目资金支持。

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B Cell Maintenance of Subcapsular Sinus Macrophages Protects against a Fatal Viral Infection Independent of Adaptive Immunity

E. Ashley Moseman1, 8, Matteo Iannacone1, 2, 8, , , Lidia Bosurgi1, 3, Elena Tonti1, 2, Nicolas Chevrier4, 5, Alexei Tumanov6, Yang-Xin Fu7, Nir Hacohen4, 5, Ulrich H. von Andrian1

Neutralizing antibodies have been thought to be required for protection against acutely cytopathic viruses, such as the neurotropic vesicular stomatitis virus (VSV). Utilizing mice that possess B cells but lack antibodies, we show here that survival upon subcutaneous (s.c.) VSV challenge was independent of neutralizing antibody production or cell-mediated adaptive immunity. However, B cells were absolutely required to provide lymphotoxin (LT) α1β2, which maintained a protective subcapsular sinus (SCS) macrophage phenotype within virus draining lymph nodes (LNs). Macrophages within the SCS of B cell-deficient LNs, or of mice that lack LTα1β2 selectively in B cells, displayed an aberrant phenotype, failed to replicate VSV, and therefore did not produce type I interferons, which were required to prevent fatal VSV invasion of intranodal nerves. Thus, although B cells are essential for survival during VSV infection, their contribution involves the provision of innate differentiation and maintenance signals to macrophages, rather than adaptive immune mechanisms.

http://www.sciencedirect.com/sci ... i/S107476131200057X